A Study to Evaluate the Safety and Efficacy of Tocilizuma... | NCT04320615

ID	Type	Description	Link
2020-001154-22	EudraCT Number

Label	Type	Description	Intervention Names
Tocilizumab (TCZ) Arm	Experimental	Participants will receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose may be given if clinical symptoms worsen or show no improvement.	Drug: Tocilizumab (TCZ)
Placebo Arm	Placebo Comparator	Participants will receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen or show no improvement.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Tocilizumab (TCZ)	Drug	Participants will receive 1 dose of IV TCZ. 1 additional dose may be given if clinical symptoms worsen or show no improvement.	Tocilizumab (TCZ) Arm

Measure	Description	Time Frame
Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4)	Clinical status was assessed using a 7-category ordinal scale: - Discharged (or "ready for discharge") - Non- intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen - Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen - ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen - ICU, requiring intubation and mechanical ventilation - ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support - Death	Day 28

Measure	Description	Time Frame
Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours	Defined as time from first dose of study drug to at least two NEWS2 assessments with a score of <=2 covering a span of at least 21.5 hours, with a maximum of 26.5 hours between the first and last of these assessments and no assessments with a score >2 in between. If one of the components of the NEWS2 score was missing at a particular time point, then the NEWS2 score was not calculated. Participants who died were censored at Day 28.

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of California San Diego		La Jolla	California	92093	United States
eStudySite

PubMed Identifier	Type	Citation	Retractions
35475258	Derived	Rosas IO, Brau N, Waters M, Go RC, Malhotra A, Hunter BD, Bhagani S, Skiest D, Savic S, Douglas IS, Garcia-Diaz J, Aziz MS, Cooper N, Youngstein T, Sorbo LD, Zerda DJ, Ustianowski A, Gracian AC, Blyth KG, Carratala J, Francois B, Benfield T, Haslem D, Bonfanti P, van der Leest CH, Rohatgi N, Wiese L, Luyt CE, Bauer RN, Cai F, Lee IT, Matharu B, Metcalf L, Wildum S, Graham E, Tsai L, Bao M. Tocilizumab in patients hospitalised with COVID-19 pneumonia: Efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA). EClinicalMedicine. 2022 May;47:101409. doi: 10.1016/j.eclinm.2022.101409. Epub 2022 Apr 21.
34612846

ID	Title	Description
FG000	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 11, 2020	Jun 23, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4)

Clinical status was assessed using a 7-category ordinal scale:

- Discharged (or "ready for discharge")
- Non- intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
- Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
- ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
- ICU, requiring intubation and mechanical ventilation
- ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support
- Death

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Number

Percentage of Participants

Day 28

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Units	Counts
Participants	OG000294 OG001144

Title

Denominators

Categories

Title	Measurements
	OG00056.5 OG00149.3

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Van Elteren Test		0.3600		Median Difference (Final Values)	-1.0			2-Sided	95	-2.5	0.0					Other

Secondary

Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours

Defined as time from first dose of study drug to at least two NEWS2 assessments with a score of <=2 covering a span of at least 21.5 hours, with a maximum of 26.5 hours between the first and last of these assessments and no assessments with a score >2 in between. If one of the components of the NEWS2 score was missing at a particular time point, then the NEWS2 score was not calculated. Participants who died were censored at Day 28.

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Median

95% Confidence Interval

Days

Up to Day 28

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Secondary

Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status

Time to improvement for this outcome measure was defined as the days from the first dose of study drug to when at least a 2-category improvement in clinical status (based on a 7-category ordinal scale) is observed. Participants who died were censored at Day 28.

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Median

95% Confidence Interval

Days

Up to Day 28

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Secondary

Time to Hospital Discharge or "Ready for Discharge"

Time to Hospital Discharge was defined as the time from the first dose of study drug to hospital discharge or "ready for discharge" (normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or \

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Median

95% Confidence Interval

Days

Up to Day 28

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Secondary

Incidence of Mechanical Ventilation by Day 28

Participants who died by Day 28 were assumed to have required mechanical ventilation.

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to Day 28

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG002	TCZ - No Mechanical Ventilation at Baseline	Participants randomized to the TCZ arm who received any amount of study drug and were not on mechanical ventilation at baseline. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Secondary

Ventilator-Free Days to Day 28

Participants who died by Day 28 were assigned 0 ventilator-free days.

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Median

95% Confidence Interval

Days

Up to Day 28

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Units	Counts
Participants

Secondary

Incidence of Intensive Care Unit (ICU) Stay by Day 28 (Week 4)

Participants who died by Day 28 were assumed to have required an ICU stay.

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to Day 28

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG002	TCZ - Not in ICU at Baseline	Participants randomized to the TCZ arm who received any amount of study drug and were not in the ICU at baseline. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Secondary

Duration of ICU Stay to Day 28 (Week 4)

Participants who died by Day 28 were assigned a duration from the first dose of study drug to Day 28 at hour 23:59:59.

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Median

95% Confidence Interval

Days

Up to Day 28

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Units	Counts
Participants

Secondary

Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14

Clinical status was assessed using a 7-category ordinal scale:

- Discharged (or "ready for discharge")
- Non- intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
- Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
- ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
- ICU, requiring intubation and mechanical ventilation
- ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support
- Death

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Number

Percentage of participants

Day 14

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Secondary

Time to Clinical Failure to Day 28 (Week 4)

Time to clinical failure was defined as the number of days from the first dose of study drug to the first occurrence on study of death, mechanical ventilation, ICU admission, or study withdrawal prior to discharge, whichever occurs first.

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Median

95% Confidence Interval

Days

Up to Day 28

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Secondary

Mortality Rate at Day 28 (Week 4)

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Number

95% Confidence Interval

Percentage of Participants

Day 28

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Units	Counts
Participants

Secondary

Time to Recovery to Day 28 (Week 4)

Time to recovery was defined as the number of days from the first dose of study drug to hospital discharge or "ready for discharge" (normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or \

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Median

95% Confidence Interval

Days

Up to Day 28

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Secondary

Duration of Supplemental Oxygen to Day 28 (Week 4)

Participants who died by Day 28 were assigned a duration of 28 days of supplemental oxygen.

mITT population: Defined as all randomized participants who received any amount of study medication, with participants grouped according to the treatment assigned at randomization.

Posted

Median

95% Confidence Interval

Days

Up to Day 28

ID	Title	Description
OG000	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
OG001	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Coagulopathy	Blood and lymphatic system disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Eosinophilia	Blood and lymphatic system disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0014 events4 affected295 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0011 events1 affected295 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0011 events1 affected295 at risk
Angina unstable	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Atrial fibrillation	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0013 events3 affected295 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Bradycardia	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Bundle branch block right	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Cardiac arrest	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0006 events5 affected143 at risk EG0014 events4 affected295 at risk
Cardiac ventricular thrombosis	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0012 events2 affected295 at risk
Left ventricular failure	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Pulseless electrical activity	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0002 events2 affected143 at risk EG0012 events2 affected295 at risk
Stress cardiomyopathy	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Ventricular arrhythmia	Cardiac disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Abdominal hernia perforation	Gastrointestinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Melaena	Gastrointestinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0012 events2 affected295 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Retroperitoneal haemorrhage	Gastrointestinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0012 events2 affected295 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0015 events5 affected295 at risk
Pyrexia	General disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Ischaemic hepatitis	Hepatobiliary disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Bacteraemia	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0003 events3 affected143 at risk EG0013 events3 affected295 at risk
Bacterial sepsis	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0013 events3 affected295 at risk
Bronchitis	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
COVID-19	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0002 events2 affected143 at risk EG00114 events14 affected295 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG00020 events20 affected143 at risk EG00136 events36 affected295 at risk
Candida infection	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Cytomegalovirus hepatitis	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Device related infection	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Empyema	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Enterobacter pneumonia	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0011 events1 affected295 at risk
Escherichia infection	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Infection	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Osteomyelitis	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Pneumonia	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0005 events4 affected143 at risk EG0018 events7 affected295 at risk
Pneumonia bacterial	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0002 events2 affected143 at risk EG0016 events6 affected295 at risk
Pneumonia escherichia	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0011 events1 affected295 at risk
Pseudomonal sepsis	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Sepsis	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0004 events4 affected143 at risk EG0013 events3 affected295 at risk
Septic shock	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0008 events7 affected143 at risk EG0017 events7 affected295 at risk
Staphylococcal infection	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0011 events1 affected295 at risk
Stenotrophomonas infection	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Streptococcal bacteraemia	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Tracheobronchitis bacterial	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Urinary tract infection	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0012 events2 affected295 at risk
Urosepsis	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0011 events1 affected295 at risk
Fall	Injury, poisoning and procedural complications	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Transfusion-related acute lung injury	Injury, poisoning and procedural complications	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Aspartate aminotransferase increased	Investigations	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Citrobacter test positive	Investigations	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Enterococcus test positive	Investigations	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Hepatic enzyme increased	Investigations	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Acidosis	Metabolism and nutrition disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Compartment syndrome	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Cerebral infarction	Nervous system disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Haemorrhagic transformation stroke	Nervous system disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Seizure	Nervous system disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0011 events1 affected295 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Delirium	Psychiatric disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0012 events2 affected295 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA v23.0	Non-systematic Assessment	EG0004 events4 affected143 at risk EG00110 events10 affected295 at risk
Renal failure	Renal and urinary disorders	MedDRA v23.0	Non-systematic Assessment	EG0002 events2 affected143 at risk EG0012 events2 affected295 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0002 events2 affected143 at risk EG0014 events4 affected295 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0002 events2 affected143 at risk EG0012 events2 affected295 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Haemothorax	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0012 events1 affected295 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0003 events3 affected143 at risk EG0010 events0 affected295 at risk
Lung consolidation	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Obstructive airways disorder	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0010 events0 affected295 at risk
Pharyngeal haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0002 events2 affected143 at risk EG0010 events0 affected295 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0003 events3 affected143 at risk EG0015 events4 affected295 at risk
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0002 events2 affected143 at risk EG0015 events5 affected295 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0006 events6 affected143 at risk EG0015 events5 affected295 at risk
Arterial haemorrhage	Vascular disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Deep vein thrombosis	Vascular disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Haematoma	Vascular disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Haemorrhage	Vascular disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Hypertension	Vascular disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Hypotension	Vascular disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0011 events1 affected295 at risk
Peripheral embolism	Vascular disorders	MedDRA v23.0	Non-systematic Assessment	EG0000 events0 affected143 at risk EG0011 events1 affected295 at risk
Shock haemorrhagic	Vascular disorders	MedDRA v23.0	Non-systematic Assessment	EG0001 events1 affected143 at risk EG0012 events2 affected295 at risk

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo Arm (Safety-Evaluable Population)	The safety-evaluable population consisted of all participants who received any amount of study medication. Participants are grouped according to the treatment first received rather than the treatment assigned at randomization.	36	143	64	143	29	143
EG001	Tocilizumab (TCZ) Arm (Safety-Evaluable Population)	The safety-evaluable population consisted of all participants who received any amount of study medication. Participants are grouped according to the treatment first received rather than the treatment assigned at randomization.	72	295	116	295	83	295

ID	Title	Description
BG000	Placebo Modified Intent-to-Treat (mITT) Arm	Participants randomized to the placebo arm who received any amount of study drug. Participants randomized to the placebo arm were to receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
BG001	Tocilizumab (TCZ) mITT Arm	Participants randomized to the TCZ arm who received any amount of study drug. Participants randomized to the TCZ arm were to receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose could be given if clinical symptoms worsened or showed no improvement.
BG002	Total	Total of all reporting groups

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA v23.0	Non-systematic Assessment	EG00010 events10 affected143 at risk EG00117 events17 affected295 at risk
Constipation	Gastrointestinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0008 events8 affected143 at risk EG00118 events18 affected295 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA v23.0	Non-systematic Assessment	EG0003 events3 affected143 at risk EG00118 events18 affected295 at risk
Pneumonia	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG00012 events8 affected143 at risk EG00110 events10 affected295 at risk
Urinary tract infection	Infections and infestations	MedDRA v23.0	Non-systematic Assessment	EG0006 events5 affected143 at risk EG00122 events22 affected295 at risk
Hypertension	Vascular disorders	MedDRA v23.0	Non-systematic Assessment	EG0004 events3 affected143 at risk EG00124 events20 affected295 at risk